PROJECT ABSTRACT Wet Age-related Macular Degeneration (AMD) is the leading cause of new blindness among people who are 55 or older. The current standard of care for wet AMD is anti-Vascular Endothelial Growth Factor (VEGF) agents, such as Lucentis, Eylea, and Avastin (used off-label). These anti-VEGF agents inhibit VEGF-mediated angiogenesis, and effectively stop or even reverse the vision loss for most patients. Despite being the best treatment currently available, it has two critical shortcomings: 1) limited near-term vision gain and poor long- term vision maintenance; (2) major cost and treatment burden. First, despite continued treatment, only ~1/3 of the patient gain >3 lines of vision over the first 12 months; after 3-4 years, most patients start losing vision again and eventually dropping to pre-treatment levels. Second, patients must return to the clinic every 1 to 2 months for intravitreal injections ? a specialized, uncomfortable and costly procedure that represents significant treatment burden. The purpose of this SBIR is to develop highly stable aptamers against SDF-1, which may serve as an orthogonal treatment for wet AMD. SDF-1 has long been known to play an important role in choroidal neovascularization (CNV), the landmark pathological process of wet AMD. The Aptitude team has accumulated extensive experience in aptamer discovery. We have previously developed the Particle Display method that significantly improves the aptamer performance. Moreover, we have made further improvement to directly screen for fully modified aptamers that enables longer duration of efficacy. Our expertise in aptamer discovery is complemented by our collaborators? expertise in wet AMD preclinical research. Our collaborator is among the first to demonstrate the role of SDF-1 in CNV, and possess in-depth expertise in relevant animal models. If successful, this project has the potential of bringing more efficacious and affordable treatment to wet AMD patients.